Analysis of the ets-1 and ets-2 genes has revealed much molecular and biochemical information. The functions of these proto-oncogenes during development, differentiation and transformation remains to be determined. The transgenic mouse system will be utilized to study specific functions of the murine ets-I and ets-2 genes. Four approaches are being studied: first, 5' regulatory regions for the ets genes will be defined using varying lengths of the 5' regulatory regions controlling expression of the lacZ reporter gene; second, mice will be made incapable of producing ets-I by mutating this gene through the use of homologous recombination in embryonic stem cells; third, the specificity of developmental and differentiating functions of the ets genes will be analyzed by altering the control of their expression through the use of chimeric genes in which the cDNA of one gene is expressed using the regulatory control elements of the other gene. Finally, further functional information will be obtained by studying the effects of the overexpression of ets-I and ets-2 in various tissues of transgenic animals by misdirecting the expression of these genes through the use of heterologous promoters.